The overall goals of this program are to (1) learn more of the biology of human normal replicating and malignant cells, (2) investigate the effects of drugs, biological modifiers and heat on these cells, and (3) as a result investigate and develop new or improved therapy for malignant disease in man. While the major emphasis of this program is the use of drugs to treat human disease, new projects are described that involve biological modifiers (e.g, interferon) and hyperthermia (local or whole body), alone, and in combination with drugs. Specific projects include investigations and treatment of acute leukemia, folate antagonist chemotherapy, rational design of drug combinations, prevention of adriamycin cardiotoxicity, the role of polyamines in cell differentiation, growth of human tumor stem cells in vitro and in vivo, studies of myeloma and melanoma, receptor studies in breast and gynecologic malignancies, solid tumor chemotherapy programs, and supportive care investigations.